Healthy
Conditions
Keywords
Healthy Volunteers
Brief summary
This was a double-blind, randomized, placebo- and positive-controlled, parallel group, 3-arm study that assessed the potential for therapeutic and supratherapeutic concentrations of setmelanotide to affect the QTc corrected by the Fredericia method (QTcF) interval.
Interventions
DRUGSetmelanotide
Administered once daily via SC injection.
DRUGMoxifloxacin
Moxifloxacin capsules via oral administration.
DRUGOral Placebo
Placebo capsules via oral administration.
DRUGSC Placebo
Placebo via SC injection.
Sponsors
Rhythm Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant has body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m\^2), inclusive. * Participant is in good health, as confirmed by no clinically significant findings from medical history, physical examination, 12-lead Electrocardiogram (ECG), vital signs measurements, clinical laboratory evaluations, and liver function tests at Screening and Check-in. * Female participants of childbearing potential must be confirmed non-pregnant and agree to use contraception. * Male participants with female partners of childbearing potential must agree to use contraception. Male participants must also not donate sperm during and for 90 days following their participation in the study. * Participant is a nonsmoker (for at least 3 months) with negative urinary cotinine test at Screening and agrees to abstain from alcohol, recreational drugs (including marijuana), and tobacco or nicotine-containing products for the duration of the study. * Participant is able to comprehend and is willing to sign an informed consent form and abide by the study restrictions.
Exclusion criteria
* Participant has sustained systolic blood pressure (SBP) \>150 millimeters of mercury (mmHg) or \<90 mmHg or a diastolic blood pressure (DBP) \>100 mmHg or \<60 mmHg in the supine position at Screening or Day 1 of each study period, respectively. * Participant has supine pulse rate of \<45 beats per minute (bpm) or \>100 bpm. * Participant has abnormal screening ECG indicating a second- or third-degree atrioventricular block, or one or more of the following: QRS\>110 millisecond (msec) , QTcF \>450 msec for males and \>470 msec for females, PR interval \>200 msec. * Participant has a history of risk factors for Torsades de Pointes (TdP), including unexplained syncope, diagnosis or family history of Brugada syndrome or long QT syndrome, heart failure, myocardial infarction, angina, or clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesaemia. * Glomerular filtration rate (GFR) \<60 milliliter per minute (mL/min) at Screening. * Participant has significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion). * Participant has history or close family history (parents or siblings) of melanoma or participant history of ocular-cutaneous albinism. * Participant has significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, or psychiatric disorder (as determined by the Investigator). * Participant has suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening, a history of a suicide attempt in the last 20 years, or any suicidal behavior in the last month. * Participant has participated in any clinical study with an investigational drug/device within 30 days (or 5 half-lives) prior to the first day of dosing. * Participant was previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide. * Participant has inability to comply with once daily dosing (QD) injection regimen. * Female participants who are breastfeeding or nursing. * Participant has cognitive impairment that, in the investigator's opinion, precludes participation to the study. * Participant is, in investigator's opinion, otherwise not suitable to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hours (hrs) postdose | Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Baseline and Day 10. ECG analysts were blinded to the treatment, timepoint and participant. QT interval was corrected for heart rate using QTcF. CHFB in QTcF was calculated at each timepoint. |
| Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose | Continuous 12-lead digital ECG recording was performed on Baseline and Day 16. ECG analysts were blinded to the treatment, timepoint and participant. QT interval was corrected for heart rate using QTcF. CHFB in QTcF was calculated at each timepoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose | The CHFB in QTcF was analyzed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate. |
| Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose | The CHFB in QTcF was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate. |
| Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose | The CHFB in PR was analyzed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate. |
| Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose | The CHFB in PR was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate. |
| Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose | The CHFB in QRS was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate. |
| Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose | The CHFB in QRS was analyzed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate. |
| Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hours (hrs) postdose | The CHFB in HR was analyzed using an analysis of variance model (ANOVA) including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate. Placebo corrected values were reported in the inferential statistics. |
| Number of Participants With at Least One Treatment-Emergent Abnormal Value in PR Intervals After Administration of SC Setmelanotide | Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg) | A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: PR (\>220 msec, Relative CHFB \>25%); Relative CHFB = 100\*(Value-Baseline)/Baseline |
| Number of Participants With at Least One Treatment-Emergent Abnormal Value in QRS Intervals After Administration of SC Setmelanotide | Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg) | A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: QRS ( \>120 msec, Relative CHFB \>25%); Relative CHFB = 100\*(Value-Baseline)/Baseline |
| Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg) | A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: QTcF (450\<QTc\<=480 msec, 480\<QTc\<=500 msec, QTc\>500 msec, 30\<CHFB in QTc\<=60 msec, CHFB in \>60 msec) |
| Number of Participants With at Least One Treatment-Emergent Abnormal Finding in T-wave Morphology and U-wave Presence After Administration of SC Setmelanotide | Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg) | A treatment-emergent abnormality/finding will be defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included : QTcF Increase From Baseline, \> 30 msec And \< 60 msec |
| Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose | Continuous 12-lead digital ECG recording was performed on Baseline and Day 10. ECG analysts were blinded to the treatment, timepoint and participant. CHFB in QTcF was calculated at each timepoint. |
| Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose | Continuous 12-lead digital ECG recording was performed on Baseline and Day 16. ECG analysts were blinded to the treatment, timepoint and participant. CHFB in QTcF was calculated at each timepoint. |
| Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide | Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg) | A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: HR (\<40 beats/min, HR\>120 beats/min and Relative CHFB \>25%) Relative CHFB = 100\*(Value-Baseline)/Baseline |
| Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose | The CHFB in HR was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate. |
Countries
United States
Participant flow
Recruitment details
77 healthy participants aged 18 to 50 years, inclusive, were enrolled in the United States.
Pre-assignment details
Participants were randomized 1:1:1 into Group 1, 2, or 3.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Setmelanotide 2-7 mg + Placebo for Moxifloxacin Participants received titrated doses of 2-7 mg setmelanotide once daily by SC injection, starting with a dose of 2 mg from Days 1 to 7, 3 mg from Days 8 to 10, 5 mg from Days 11 to 13 and 7 mg from Days 14 to 16. Participants also received single oral dose of placebo matching moxifloxacin on Days 10 and 16. | 28 |
| Group 2: Placebo for Setmelanotide + Moxifloxacin 400 mg + Placebo for Moxifloxacin Participants received placebo matching setmelanotide once daily by SC injection from Days 1 to 16. Participants also received a single oral dose of 400 mg moxifloxacin on Day 10 and a single oral dose of placebo matching moxifloxacin on Day 16. | 24 |
| Group 3: Placebo for Setmelanotide + Placebo for Moxifloxacin + Moxifloxacin 400 mg Participants received placebo matching setmelanotide once daily by SC injection from Days 1 to 16. Participants also received a single oral dose of placebo matching moxifloxacin on Day 10 and a single oral dose of 400 mg moxifloxacin on Day 16. | 25 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 | 0 |
| Overall Study | Positive Covid19 Result. | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Group 1: Setmelanotide 2-7 mg + Placebo for Moxifloxacin | Group 2: Placebo for Setmelanotide + Moxifloxacin 400 mg + Placebo for Moxifloxacin | Group 3: Placebo for Setmelanotide + Placebo for Moxifloxacin + Moxifloxacin 400 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 31.9 years STANDARD_DEVIATION 6.47 | 36.1 years STANDARD_DEVIATION 9.28 | 34.8 years STANDARD_DEVIATION 8.6 | 34.2 years STANDARD_DEVIATION 8.22 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 9 Participants | 10 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 15 Participants | 15 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 5 Participants | 8 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) White | 13 Participants | 13 Participants | 12 Participants | 38 Participants |
| Sex: Female, Male Female | 10 Participants | 11 Participants | 12 Participants | 33 Participants |
| Sex: Female, Male Male | 18 Participants | 13 Participants | 13 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 24 | 0 / 23 | 0 / 21 | 0 / 24 | 0 / 23 | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 25 / 28 | 16 / 24 | 17 / 23 | 9 / 21 | 18 / 24 | 17 / 23 | 15 / 25 | 4 / 25 |
| serious Total, serious adverse events | 1 / 28 | 0 / 24 | 0 / 23 | 0 / 21 | 0 / 24 | 0 / 23 | 0 / 25 | 0 / 25 |
Outcome results
Primary
Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10
Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Baseline and Day 10. ECG analysts were blinded to the treatment, timepoint and participant. QT interval was corrected for heart rate using QTcF. CHFB in QTcF was calculated at each timepoint.
Time frame: Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hours (hrs) postdose
Population: Pharmacokinetic (PK)/QTc Population included participants who were in both ECG \& PK populations. PK Population included all participants who received at least 1 dose of setmelanotide or moxifloxacin \& have at least 1 quantifiable concentration of setmelanotide or moxifloxacin. ECG Population included all participants in safety population with measurements at baseline as well as on-treatment with at least one post-dose timepoint with a valid value. Participants with available data were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 0.5 hr Post dose | -3.6 milliseconds (msec) | Standard Deviation 9.83 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 6 hr Post dose | -0.4 milliseconds (msec) | Standard Deviation 9.71 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 2.5 hr Post dose | 1.2 milliseconds (msec) | Standard Deviation 11.22 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 7 hr Post dose | 1.0 milliseconds (msec) | Standard Deviation 8.02 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 1.5 hr Post dose | -3.0 milliseconds (msec) | Standard Deviation 9.53 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 8 hr Post dose | 2.6 milliseconds (msec) | Standard Deviation 9.11 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 3 hr Post dose | 2.1 milliseconds (msec) | Standard Deviation 10.06 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 9 hr Post dose | 4.1 milliseconds (msec) | Standard Deviation 7.84 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 1 hr Post dose | -2.9 milliseconds (msec) | Standard Deviation 12.69 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 10 hr Post dose | 5.0 milliseconds (msec) | Standard Deviation 8.14 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 4 hr Post dose | 2.0 milliseconds (msec) | Standard Deviation 9.76 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 12 hr Post dose | 1.9 milliseconds (msec) | Standard Deviation 9.25 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 2 hr Post dose | -1.0 milliseconds (msec) | Standard Deviation 11.26 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 16 hr Post dose | 1.7 milliseconds (msec) | Standard Deviation 7.46 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 5 hr Post dose | 2.4 milliseconds (msec) | Standard Deviation 9.38 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 24 hr Post dose | -0.7 milliseconds (msec) | Standard Deviation 13.32 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | Predose | 1.9 milliseconds (msec) | Standard Deviation 7.82 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 24 hr Post dose | 1.6 milliseconds (msec) | Standard Deviation 8.28 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | Predose | -1.5 milliseconds (msec) | Standard Deviation 5.25 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 0.5 hr Post dose | -3.5 milliseconds (msec) | Standard Deviation 8.16 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 1 hr Post dose | -3.5 milliseconds (msec) | Standard Deviation 5.87 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 1.5 hr Post dose | -3.2 milliseconds (msec) | Standard Deviation 7.44 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 2 hr Post dose | -3.4 milliseconds (msec) | Standard Deviation 5.7 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 2.5 hr Post dose | -2.0 milliseconds (msec) | Standard Deviation 8.92 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 3 hr Post dose | -2.6 milliseconds (msec) | Standard Deviation 6.75 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 4 hr Post dose | -2.4 milliseconds (msec) | Standard Deviation 8.09 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 5 hr Post dose | 0.2 milliseconds (msec) | Standard Deviation 8.99 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 6 hr Post dose | -1.8 milliseconds (msec) | Standard Deviation 6.88 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 7 hr Post dose | -1.3 milliseconds (msec) | Standard Deviation 7.36 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 8 hr Post dose | -0.3 milliseconds (msec) | Standard Deviation 7.93 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 9 hr Post dose | -2.0 milliseconds (msec) | Standard Deviation 6.58 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 10 hr Post dose | -0.9 milliseconds (msec) | Standard Deviation 9.96 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 12 hr Post dose | 3.4 milliseconds (msec) | Standard Deviation 8.65 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected Change From Baseline (CHFB) in Fridericia's Correction (QTcF) at Day 10 | 16 hr Post dose | -1.0 milliseconds (msec) | Standard Deviation 7.64 |
Comparison: The C-QTc analysis was performed with a non-linear model.~The mean of placebo-corrected CHFB in QTcF at maximum concentration (Cmax) geometric mean of therapeutic dose (3 mg QD) was estimated with bias-corrected 90% CI by nonparametric bootstrap methods.90% CI: [1.23, 6.17]
Primary
Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16
Continuous 12-lead digital ECG recording was performed on Baseline and Day 16. ECG analysts were blinded to the treatment, timepoint and participant. QT interval was corrected for heart rate using QTcF. CHFB in QTcF was calculated at each timepoint.
Time frame: Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose
Population: PK/QTc Population included participants who were in both ECG \& PK populations. PK Population included all participants who received at least 1 dose of setmelanotide or moxifloxacin and have at least one quantifiable concentration of setmelanotide or moxifloxacin. ECG Population included all participants in safety population with measurements at baseline as well as on-treatment with at least one post-dose timepoint with a valid value. Participants with available data were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 8 hr Post dose | 2.8 msec | Standard Deviation 10.02 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 4 hr Post dose | 3.6 msec | Standard Deviation 9.88 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 1 hr Post dose | 1.6 msec | Standard Deviation 9.18 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 5 hr Post dose | 4.7 msec | Standard Deviation 9.41 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | Predose | 4.5 msec | Standard Deviation 6.49 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 6 hr Post dose | 2.8 msec | Standard Deviation 9.64 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 1.5 hr Post dose | 0.3 msec | Standard Deviation 10.42 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 7 hr Post dose | 1.5 msec | Standard Deviation 11.14 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 9 hr Post dose | 6.1 msec | Standard Deviation 8.72 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 10 hr Post dose | 6.5 msec | Standard Deviation 6.64 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 2 hr Post dose | 2.2 msec | Standard Deviation 10.94 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 12 hr Post dose | 5.8 msec | Standard Deviation 7.96 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 0.5 hr Post dose | 1.0 msec | Standard Deviation 8.83 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 16 hr Post dose | 1.4 msec | Standard Deviation 7.77 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 3 hr Post dose | 4.3 msec | Standard Deviation 11.34 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 24 hr Post dose | 1.0 msec | Standard Deviation 11.26 |
| Group 1: Setmelanotide 3 mg | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 2.5 hr Post dose | 2.7 msec | Standard Deviation 11.61 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 24 hr Post dose | -5.6 msec | Standard Deviation 9.67 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 2.5 hr Post dose | -2.5 msec | Standard Deviation 9.09 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 8 hr Post dose | -2.6 msec | Standard Deviation 8.27 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 9 hr Post dose | -1.2 msec | Standard Deviation 7 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | Predose | -2.3 msec | Standard Deviation 8.24 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 0.5 hr Post dose | -5.2 msec | Standard Deviation 6.97 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 1 hr Post dose | -4.3 msec | Standard Deviation 8.2 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 1.5 hr Post dose | -2.9 msec | Standard Deviation 8.64 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 2 hr Post dose | -2.0 msec | Standard Deviation 8.96 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 3 hr Post dose | -2.0 msec | Standard Deviation 8.07 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 4 hr Post dose | -2.5 msec | Standard Deviation 6.37 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 5 hr Post dose | -0.5 msec | Standard Deviation 6.42 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 6 hr Post dose | -2.4 msec | Standard Deviation 7.28 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 7 hr Post dose | -2.0 msec | Standard Deviation 6.31 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 10 hr Post dose | -2.5 msec | Standard Deviation 7.14 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 12 hr Post dose | -0.4 msec | Standard Deviation 5.99 |
| Group 3: Placebo | Setmelanotide Concentration-related Placebo-corrected CHFB in QTcF at Day 16 | 16 hr Post dose | -2.6 msec | Standard Deviation 9.3 |
Comparison: The C-QTc analysis was performed with a non-linear model. The mean of placebo-corrected CHFB in QTcF at Cmax geometric mean of therapeutic dose (7 mg QD) was estimated with bias-corrected 90% CI by nonparametric bootstrap methods.90% CI: [1.7, 7.64]
Secondary
Moxifloxacin Concentration-related CHFB in QTcF at Day 10
Continuous 12-lead digital ECG recording was performed on Baseline and Day 10. ECG analysts were blinded to the treatment, timepoint and participant. CHFB in QTcF was calculated at each timepoint.
Time frame: Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose
Population: PK/QTc Population was analyzed. Participants with available data were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | Pre dose | 1.5 msec | Standard Deviation 7.76 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 0.5 hr Post dose | -5.3 msec | Standard Deviation 8.75 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 1 hr Post dose | -3.7 msec | Standard Deviation 9.39 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 1.5 hr Post dose | 0.9 msec | Standard Deviation 8.56 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 2 hr Post dose | 2.0 msec | Standard Deviation 8.74 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 2.5 hr Post dose | 4.9 msec | Standard Deviation 8.75 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 5 hr Post dose | 8.1 msec | Standard Deviation 8.42 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 6 hr Post dose | 6.0 msec | Standard Deviation 6.61 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 7 hr Post dose | 5.1 msec | Standard Deviation 8.39 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 8 hr Post dose | 4.4 msec | Standard Deviation 8.18 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 9 hr Post dose | 5.0 msec | Standard Deviation 10.47 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 10 hr Post dose | 6.2 msec | Standard Deviation 6.85 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 12 hr Post dose | 8.7 msec | Standard Deviation 4.84 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 3 hr Post dose | 4.9 msec | Standard Deviation 7.39 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 4 hr Post dose | 6.3 msec | Standard Deviation 8.63 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 16 hr Post dose | 5.9 msec | Standard Deviation 8.09 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 10 | 24 hr Post dose | 6.6 msec | Standard Deviation 8 |
Secondary
Moxifloxacin Concentration-related CHFB in QTcF at Day 16
Continuous 12-lead digital ECG recording was performed on Baseline and Day 16. ECG analysts were blinded to the treatment, timepoint and participant. CHFB in QTcF was calculated at each timepoint.
Time frame: Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose
Population: PK/QTc Population was analyzed. Participants with available data were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 6 hr Post dose | 8.5 msec | Standard Deviation 6.18 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 7 hr Post dose | 9.1 msec | Standard Deviation 7.29 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 8 hr Post dose | 8.0 msec | Standard Deviation 5.73 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 9 hr Post dose | 7.0 msec | Standard Deviation 7.33 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 10 hr Post dose | 7.0 msec | Standard Deviation 9.93 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 24 hr Post dose | 4.4 msec | Standard Deviation 10.57 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | Pre dose | -0.8 msec | Standard Deviation 8.3 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 0.5 hr Post dose | -1.8 msec | Standard Deviation 5.93 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 1 hr Post dose | -1.9 msec | Standard Deviation 7.49 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 1.5 hr Post dose | 3.0 msec | Standard Deviation 7.05 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 2 hr Post dose | 4.2 msec | Standard Deviation 7.53 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 2.5 hr Post dose | 7.6 msec | Standard Deviation 8.45 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 3 hr Post dose | 8.1 msec | Standard Deviation 8.19 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 4 hr Post dose | 8.8 msec | Standard Deviation 6.37 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 5 hr Post dose | 7.5 msec | Standard Deviation 8.97 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 12 hr Post dose | 10.8 msec | Standard Deviation 9.14 |
| Group 1: Setmelanotide 3 mg | Moxifloxacin Concentration-related CHFB in QTcF at Day 16 | 16 hr Post dose | 6.6 msec | Standard Deviation 8.51 |
Secondary
Number of Participants With at Least One Treatment-Emergent Abnormal Finding in T-wave Morphology and U-wave Presence After Administration of SC Setmelanotide
A treatment-emergent abnormality/finding will be defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included : QTcF Increase From Baseline, \> 30 msec And \< 60 msec
Time frame: Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)
Population: ECG population with available data was analyzed. ECG data was collected on Days 10 and 16, where participants received setmelanotide 3 mg and 7 mg respectively.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Finding in T-wave Morphology and U-wave Presence After Administration of SC Setmelanotide | 1 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Finding in T-wave Morphology and U-wave Presence After Administration of SC Setmelanotide | 1 Participants |
Secondary
Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide
A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: HR (\<40 beats/min, HR\>120 beats/min and Relative CHFB \>25%) Relative CHFB = 100\*(Value-Baseline)/Baseline
Time frame: Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)
Population: ECG population with available data was analyzed. ECG data was collected on Days 10 and 16, where participants received setmelanotide 3 mg and 7 mg respectively.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide | Relative CHFB in HR>25% | 4 Participants |
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide | HR<40 beats/min | 0 Participants |
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide | HR>120 beats/min | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide | HR>120 beats/min | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide | Relative CHFB in HR>25% | 9 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in HR Intervals After Administration of SC Setmelanotide | HR<40 beats/min | 0 Participants |
Secondary
Number of Participants With at Least One Treatment-Emergent Abnormal Value in PR Intervals After Administration of SC Setmelanotide
A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: PR (\>220 msec, Relative CHFB \>25%); Relative CHFB = 100\*(Value-Baseline)/Baseline
Time frame: Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)
Population: ECG Population with available data was analyzed. ECG data was collected on Days 10 and 16, where participants received setmelanotide 3 mg and 7 mg respectively.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in PR Intervals After Administration of SC Setmelanotide | PR>220 msec | 0 Participants |
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in PR Intervals After Administration of SC Setmelanotide | Relative CHFB in PR>25% | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in PR Intervals After Administration of SC Setmelanotide | PR>220 msec | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in PR Intervals After Administration of SC Setmelanotide | Relative CHFB in PR>25% | 0 Participants |
Secondary
Number of Participants With at Least One Treatment-Emergent Abnormal Value in QRS Intervals After Administration of SC Setmelanotide
A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: QRS ( \>120 msec, Relative CHFB \>25%); Relative CHFB = 100\*(Value-Baseline)/Baseline
Time frame: Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)
Population: ECG Population with available data was analyzed. ECG data was collected on Days 10 and 16, where participants received setmelanotide 3 mg and 7 mg respectively.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QRS Intervals After Administration of SC Setmelanotide | QRS>120 msec | 0 Participants |
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QRS Intervals After Administration of SC Setmelanotide | Relative CHFB in QRS>25% | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QRS Intervals After Administration of SC Setmelanotide | QRS>120 msec | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QRS Intervals After Administration of SC Setmelanotide | Relative CHFB in QRS>25% | 0 Participants |
Secondary
Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide
A treatment-emergent abnormality/finding was defined as any abnormality/finding not already reported on any of the ECGs collected before the administration. Abnormal findings included: QTcF (450\<QTc\<=480 msec, 480\<QTc\<=500 msec, QTc\>500 msec, 30\<CHFB in QTc\<=60 msec, CHFB in \>60 msec)
Time frame: Day 10 (for setmelanotide 3 mg) and Day 16 (for setmelanotide 7mg)
Population: ECG Population with available data was analyzed. ECG data was collected on Days 10 and 16, where participants received setmelanotide 3 mg and 7 mg respectively.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | 480<QTc<=500 msec | 0 Participants |
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | 30<CHFB in QTc<=60 msec | 0 Participants |
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | QTc>500 msec | 0 Participants |
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | CHFB in QTc>60 msec | 0 Participants |
| Group 1: Setmelanotide 3 mg | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | 450<QTc<=480 msec | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | CHFB in QTc>60 msec | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | 450<QTc<=480 msec | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | 480<QTc<=500 msec | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | QTc>500 msec | 0 Participants |
| Group 3: Placebo | Number of Participants With at Least One Treatment-Emergent Abnormal Value in QTcF Intervals After Administration of SC Setmelanotide | 30<CHFB in QTc<=60 msec | 0 Participants |
Secondary
Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10
The CHFB in HR was analyzed using an analysis of variance model (ANOVA) including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate. Placebo corrected values were reported in the inferential statistics.
Time frame: Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hours (hrs) postdose
Population: ECG population with available data was analyzed. ECG data was collected on Day 10 where participants received setmelanotide 3 mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 16 hr Post dose | 1.7 beats per minute (bpm) | Standard Deviation 6.93 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1 hr Post dose | -2.7 beats per minute (bpm) | Standard Deviation 11.67 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2 hr Post dose | -2.1 beats per minute (bpm) | Standard Deviation 10.94 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2.5 hr Post dose | -1.8 beats per minute (bpm) | Standard Deviation 9.31 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 7 hr Post dose | -2.9 beats per minute (bpm) | Standard Deviation 6.45 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 24 hr Post dose | 2.1 beats per minute (bpm) | Standard Deviation 6.04 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Pre dose | 2.3 beats per minute (bpm) | Standard Deviation 9.65 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1.5 hr Post dose | -0.2 beats per minute (bpm) | Standard Deviation 13.13 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 3 hr Post dose | 0.2 beats per minute (bpm) | Standard Deviation 10.7 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 4 hr Post dose | -1.2 beats per minute (bpm) | Standard Deviation 7.91 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 5 hr Post dose | 0.6 beats per minute (bpm) | Standard Deviation 7.51 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 6 hr Post dose | -1.3 beats per minute (bpm) | Standard Deviation 7.66 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 8 hr Post dose | -2.2 beats per minute (bpm) | Standard Deviation 5.93 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 9 hr Post dose | -1.3 beats per minute (bpm) | Standard Deviation 6.34 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 10 hr Post dose | -0.8 beats per minute (bpm) | Standard Deviation 5.82 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 12 hr Post dose | -2.8 beats per minute (bpm) | Standard Deviation 7.49 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 0.5 hr Post dose | -2.0 beats per minute (bpm) | Standard Deviation 9.58 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 12 hr Post dose | 3.3 beats per minute (bpm) | Standard Deviation 6.03 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 0.5 hr Post dose | 0.9 beats per minute (bpm) | Standard Deviation 6.39 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 3 hr Post dose | -0.4 beats per minute (bpm) | Standard Deviation 8.47 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1 hr Post dose | 1.3 beats per minute (bpm) | Standard Deviation 5.79 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 8 hr Post dose | 2.4 beats per minute (bpm) | Standard Deviation 7.04 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2 hr Post dose | 0.0 beats per minute (bpm) | Standard Deviation 6.77 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 4 hr Post dose | -0.6 beats per minute (bpm) | Standard Deviation 6.26 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2.5 hr Post dose | 1.7 beats per minute (bpm) | Standard Deviation 6.33 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 6 hr Post dose | 3.6 beats per minute (bpm) | Standard Deviation 5.97 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 10 hr Post dose | 0.9 beats per minute (bpm) | Standard Deviation 5.33 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 16 hr Post dose | 1.9 beats per minute (bpm) | Standard Deviation 7 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 5 hr Post dose | 3.1 beats per minute (bpm) | Standard Deviation 7.36 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 24 hr Post dose | 1.3 beats per minute (bpm) | Standard Deviation 5.37 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 9 hr Post dose | 1.3 beats per minute (bpm) | Standard Deviation 6.27 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Pre dose | -0.3 beats per minute (bpm) | Standard Deviation 7.31 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 7 hr Post dose | 0.9 beats per minute (bpm) | Standard Deviation 4.74 |
| Group 3: Placebo | Placebo-corrected CHFB in Heart Rate (HR) After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1.5 hr Post dose | 2.0 beats per minute (bpm) | Standard Deviation 5.51 |
Comparison: Pre-dose90% CI: [-0.6, 5.6]
Comparison: 0.5 hr Post dose90% CI: [-3, 3.1]
Comparison: 1 hr Post dose90% CI: [-2.8, 3]
Comparison: 1.5 hr Post dose90% CI: [-1.8, 5.1]
Comparison: 2 hr Post dose90% CI: [-2.8, 4.1]
Comparison: 2.5 hr Post dose90% CI: [-2.9, 3.4]
Comparison: 3 hr Post dose90% CI: [-1.4, 5.7]
Comparison: 4 hr Post dose90% CI: [-2.9, 2.7]
Comparison: 5 hr Post dose90% CI: [-3.1, 2.7]
Comparison: 6 hr Post dose90% CI: [-3.8, 2.3]
Comparison: 7 hr Post dose90% CI: [-5.5, -0.1]
Comparison: 8 hr Post dose90% CI: [-4.5, 1.3]
Comparison: 9 hr Post dose90% CI: [-2.5, 3]
Comparison: 10 hr Post dose90% CI: [-2.3, 2.7]
Comparison: 12 hr Post dose90% CI: [-5.9, -0.1]
Comparison: 16 hr Post dose90% CI: [-5.1, 1]
Comparison: 24 hr Post dose90% CI: [-1.6, 3.8]
Comparison: Pre-dose90% CI: [-1.7, 4.5]
Comparison: 0.5 hr Post dose90% CI: [-1.4, 4.7]
Comparison: 1 hr Post dose90% CI: [-1, 4.8]
Comparison: 1.5 hr Post dose90% CI: [-0.9, 6]
Comparison: 2 hr Post dose90% CI: [-2.1, 4.8]
Comparison: 2.5 hr Post dose90% CI: [-1.4, 4.9]
Comparison: 3 hr Post dose90% CI: [-1.9, 5.1]
Comparison: 4 hr Post dose90% CI: [-1.4, 4.2]
Comparison: 5 hr Post dose90% CI: [-0.2, 5.7]
Comparison: 6 hr Post dose90% CI: [1.4, 7.5]
Comparison: 7 hr Post dose90% CI: [0.1, 5.5]
Comparison: 8 hr Post dose90% CI: [1.2, 7]
Comparison: 9 hr Post dose90% CI: [0.8, 6.3]
Comparison: 10 hr Post dose90% CI: [0.8, 5.8]
Comparison: 12 hr Post dose90% CI: [-0.3, 5.5]
Comparison: 16 hr Post dose90% CI: [-2.7, 3.4]
Comparison: 24 hr Post dose90% CI: [-1, 4.4]
Secondary
Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16
The CHFB in HR was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.
Time frame: Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose
Population: ECG population with available data was analyzed. ECG data was collected on Day 16, where participants received setmelanotide 7 mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 0.5 hr Post dose | -1.7 bpm | Standard Deviation 9.57 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 6 hr Post dose | 3.9 bpm | Standard Deviation 9.21 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1.5 hr Post dose | -1.5 bpm | Standard Deviation 10.35 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 7 hr Post dose | 1.2 bpm | Standard Deviation 6.71 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2 hr Post dose | -3.0 bpm | Standard Deviation 7.19 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 8 hr Post dose | 0.8 bpm | Standard Deviation 7.13 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2.5 hr Post dose | -0.8 bpm | Standard Deviation 7.24 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 9 hr Post dose | 1.5 bpm | Standard Deviation 7.3 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1 hr Post dose | -2.2 bpm | Standard Deviation 10.61 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 10 hr Post dose | 2.1 bpm | Standard Deviation 7.82 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 4 hr Post dose | 1.5 bpm | Standard Deviation 6.9 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 12 hr Post dose | 0.6 bpm | Standard Deviation 8 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 3 hr Post dose | -0.2 bpm | Standard Deviation 7.11 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 16 hr Post dose | 3.0 bpm | Standard Deviation 6.98 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 5 hr Post dose | 3.5 bpm | Standard Deviation 7.84 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 24 hr Post dose | 6.2 bpm | Standard Deviation 7.41 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Pre dose | 3.4 bpm | Standard Deviation 7.41 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 24 hr Post dose | 0.4 bpm | Standard Deviation 6.39 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Pre dose | -0.3 bpm | Standard Deviation 4.95 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1 hr Post dose | 0.1 bpm | Standard Deviation 5.96 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2.5 hr Post dose | 0.4 bpm | Standard Deviation 6.49 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 0.5 hr Post dose | -0.1 bpm | Standard Deviation 6.35 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1.5 hr Post dose | 1.5 bpm | Standard Deviation 5.78 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2 hr Post dose | 0.5 bpm | Standard Deviation 5.14 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 3 hr Post dose | 2.1 bpm | Standard Deviation 5.44 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 4 hr Post dose | 2.0 bpm | Standard Deviation 5.18 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 5 hr Post dose | 3.4 bpm | Standard Deviation 5.76 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 6 hr Post dose | 0.7 bpm | Standard Deviation 5.66 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 7 hr Post dose | 3.3 bpm | Standard Deviation 7.68 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 8 hr Post dose | 2.8 bpm | Standard Deviation 4.71 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 9 hr Post dose | 1.6 bpm | Standard Deviation 6.59 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 10 hr Post dose | 2.8 bpm | Standard Deviation 5.16 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 12 hr Post dose | 3.0 bpm | Standard Deviation 3.86 |
| Group 3: Placebo | Placebo-corrected CHFB in HR After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 16 hr Post dose | 3.3 bpm | Standard Deviation 4.75 |
Comparison: Pre dose90% CI: [-2.8, 3.4]
Comparison: 0.5 hr Post dose90% CI: [-5.3, 1]
Comparison: 1 hr Post dose90% CI: [-4.7, 1.4]
Comparison: 1.5 hr Post dose90% CI: [-5.3, 1]
Comparison: 2 hr Post dose90% CI: [-6.3, -0.3]
Comparison: 2.5 hr Post dose90% CI: [-4.1, 1.7]
Comparison: 3 hr Post dose90% CI: [-4.2, 1.7]
Comparison: 4 hr Post dose90% CI: [-3.6, 2.5]
Comparison: 5 hr Post dose95% CI: [-4.1, 2.1]
Comparison: 6 hr Post dose90% CI: [-2.7, 3.5]
Comparison: 7 hr Post dose90% CI: [-5.5, 0.5]
Comparison: 8 hr Post dose90% CI: [-5.2, 0.8]
Comparison: 9 hr Post dose90% CI: [-4.3, 2.6]
Comparison: 10 hr Post dose90% CI: [-3.6, 3.2]
Comparison: 12 hr Post dose90% CI: [-5.5, 1]
Comparison: 16 hr Post dose90% CI: [-5.4, 1.7]
Comparison: 24 hr Post dose90% CI: [-1.2, 6.3]
Comparison: Pre-dose90% CI: [-5.1, 0.8]
Comparison: 0.5 hr Post dose90% CI: [-3.1, 3]
Comparison: 1 hr Post dose90% CI: [-3, 2.9]
Comparison: 1.5 hr Post dose90% CI: [-3.1, 3]
Comparison: 2 hr Post dose90% CI: [-3.8, 2]
Comparison: 2.5 hr Post dose90% CI: [-2.5, 3]
Comparison: 3 hr Post dose90% CI: [-1.9, 3.7]
Comparison: 4 hr Post dose90% CI: [-2.2, 3.7]
Comparison: 5 hr Post dose90% CI: [-2.8, 3.1]
Comparison: 6 hr Post dose90% CI: [-3.9, 2]
Comparison: 7 hr Post dose90% CI: [-3.1, 2.7]
Comparison: 8 hr Post dose90% CI: [-2.7, 3.1]
Comparison: 9 hr Post dose90% CI: [-2.7, 4]
Comparison: 10 hr Post dose90% CI: [-2.3, 4.1]
Comparison: 12 hr Post dose90% CI: [-3.5, 2.8]
Comparison: 16 hr Post dose90% CI: [-3.8, 3]
Comparison: 24 hr Post dose90% CI: [-5.1, 2]
Secondary
Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10
The CHFB in PR was analyzed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.
Time frame: Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose
Population: ECG population with available data was analyzed. ECG data was collected on Day 10, where participants received setmelanotide 3 mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1.5 hr Post dose | -1.0 msec | Standard Deviation 6.24 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 9 hr Post dose | -2.3 msec | Standard Deviation 6.03 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Pre dose | -2.4 msec | Standard Deviation 6.12 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 0.5 hr Post dose | -3.8 msec | Standard Deviation 8.93 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1 hr Post dose | -1.0 msec | Standard Deviation 6.22 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2 hr Post dose | -1.0 msec | Standard Deviation 6.98 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2.5 hr Post dose | -3.1 msec | Standard Deviation 4.92 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 3 hr Post dose | -3.9 msec | Standard Deviation 7.81 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 4 hr Post dose | -1.2 msec | Standard Deviation 5.78 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 5 hr Post dose | -1.0 msec | Standard Deviation 6.61 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 6 hr Post dose | -1.7 msec | Standard Deviation 5.87 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 7 hr Post dose | -2.5 msec | Standard Deviation 4.88 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 8 hr Post dose | -1.9 msec | Standard Deviation 7.06 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 10 hr Post dose | -1.2 msec | Standard Deviation 7.06 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 12 hr Post dose | -3.9 msec | Standard Deviation 7.83 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 16 hr Post dose | -3.0 msec | Standard Deviation 7.02 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 24 hr Post dose | -6.6 msec | Standard Deviation 8.39 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 12 hr Post dose | -2.1 msec | Standard Deviation 6.05 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1.5 hr Post dose | 3.7 msec | Standard Deviation 7.04 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 8 hr Post dose | 0.3 msec | Standard Deviation 7.37 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 4 hr Post dose | 1.6 msec | Standard Deviation 8.41 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 9 hr Post dose | 0.5 msec | Standard Deviation 4.49 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 24 hr Post dose | 1.2 msec | Standard Deviation 5.65 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Pre dose | 3.1 msec | Standard Deviation 5.18 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 5 hr Post dose | 0.5 msec | Standard Deviation 5.46 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 0.5 hr Post dose | 3.4 msec | Standard Deviation 8.29 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 10 hr Post dose | -0.8 msec | Standard Deviation 6.3 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1 hr Post dose | 3.5 msec | Standard Deviation 7.33 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 6 hr Post dose | -0.2 msec | Standard Deviation 6.62 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2 hr Post dose | 3.3 msec | Standard Deviation 7.44 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 16 hr Post dose | -0.0 msec | Standard Deviation 7.24 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2.5 hr Post dose | 1.5 msec | Standard Deviation 6.53 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 7 hr Post dose | 0.3 msec | Standard Deviation 5.06 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 3 hr Post dose | 2.6 msec | Standard Deviation 6.76 |
Comparison: Pre dose90% CI: [-8.4, -2.2]
Comparison: 0.5 hr Post dose90% CI: [-5.9, 0.5]
Comparison: 1 hr Post dose90% CI: [-5.7, -0.7]
Comparison: 1.5 hr Post dose90% CI: [-3.7, 1.9]
Comparison: 2 hr Post dose90% CI: [-5.7, -0.2]
Comparison: 2.5 hr Post dose90% CI: [-6.5, -1.5]
Comparison: 3 hr Post dose90% CI: [-7.1, -1.3]
Comparison: 4 hr Post dose90% CI: [-7.4, -0.8]
Comparison: 5 hr Post dose90% CI: [-3.7, 2.1]
Comparison: 6 hr Post dose90% CI: [-6.3, -0.4]
Comparison: 7 hr Post dose90% CI: [-6, -0.5]
Comparison: 8 hr Post dose90% CI: [-4.7, 1.5]
Comparison: 9 hr Post dose90% CI: [-6.9, -1.2]
Comparison: 10 hr Post dose90% CI: [-7.6, -1]
Comparison: 12 hr Post dose90% CI: [-8.7, -2.1]
Comparison: 16 hr Post dose90% CI: [-7.4, -0.8]
Comparison: 24 hr Post dose90% CI: [-10.1, -4.2]
Comparison: Pre dose90% CI: [-2, 4.2]
Comparison: 0.5 hr Post dose90% CI: [-0.1, 6.3]
Comparison: 1 hr Post dose90% CI: [-0.1, 4.9]
Comparison: 1.5 hr Post dose90% CI: [0.2, 5.8]
Comparison: 2 hr Post dose90% CI: [-1, 4.6]
Comparison: 2.5 hr Post dose90% CI: [-1.9, 3.1]
Comparison: 3 hr Post dose90% CI: [-1, 4.8]
Comparison: 4 hr Post dose90% CI: [-3.5, 3]
Comparison: 5 hr Post dose90% CI: [-2.6, 3.2]
Comparison: 6 hr Post dose90% CI: [-4.8, 1.1]
Comparison: 7 hr Post dose90% CI: [-3.8, 1.7]
Comparison: 8 hr Post dose90% CI: [-3.6, 2.6]
Comparison: 9 hr Post dose90% CI: [-5.6, 0.2]
Comparison: 10 hr Post dose90% CI: [-6.8, -0.2]
Comparison: 12 hr Post dose90% CI: [-6.6, 0.1]
Comparison: 16 hr Post dose90% CI: [-3, 3.6]
Comparison: 24 hr Post dose90% CI: [-3, 2.9]
Secondary
Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16
The CHFB in PR was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.
Time frame: Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose
Population: ECG population with available data was analyzed. ECG data was collected on Day 16, where participants received setmelanotide 7 mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 4 hr Post dose | -1.3 msec | Standard Deviation 6.34 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1.5 hr Post dose | -2.3 msec | Standard Deviation 7.45 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 5 hr Post dose | -2.6 msec | Standard Deviation 6.7 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 0.5 hr Post dose | -4.5 msec | Standard Deviation 11.01 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 6 hr Post dose | -1.7 msec | Standard Deviation 7.99 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 8 hr Post dose | -3.1 msec | Standard Deviation 5.97 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2 hr Post dose | 0.1 msec | Standard Deviation 6.67 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 9 hr Post dose | -3.4 msec | Standard Deviation 5.08 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Pre dose | -3.5 msec | Standard Deviation 7.11 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 10 hr Post dose | -1.4 msec | Standard Deviation 6.36 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2.5 hr Post dose | -0.9 msec | Standard Deviation 7.36 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 12 hr Post dose | -1.9 msec | Standard Deviation 5.77 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1 hr Post dose | 0.4 msec | Standard Deviation 7.72 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 16 hr Post dose | -4.9 msec | Standard Deviation 6.64 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 3 hr Post dose | -2.2 msec | Standard Deviation 7.12 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 24 hr Post dose | -8.4 msec | Standard Deviation 9.21 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 7 hr Post dose | -3.7 msec | Standard Deviation 5.65 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 24 hr Post dose | 2.5 msec | Standard Deviation 7.28 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 7 hr Post dose | -1.1 msec | Standard Deviation 9.29 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Pre dose | 3.4 msec | Standard Deviation 11.46 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 0.5 hr Post dose | 3.9 msec | Standard Deviation 9.88 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1 hr Post dose | 5.8 msec | Standard Deviation 10.9 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1.5 hr Post dose | 2.4 msec | Standard Deviation 9.42 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2 hr Post dose | 2.0 msec | Standard Deviation 8.17 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2.5 hr Post dose | 3.2 msec | Standard Deviation 7.46 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 3 hr Post dose | 2.0 msec | Standard Deviation 8 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 4 hr Post dose | 1.3 msec | Standard Deviation 9.51 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 5 hr Post dose | 1.2 msec | Standard Deviation 9.99 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 8 hr Post dose | 0.8 msec | Standard Deviation 8.52 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 9 hr Post dose | 0.4 msec | Standard Deviation 7.66 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 10 hr Post dose | 1.1 msec | Standard Deviation 7.8 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 12 hr Post dose | 0.8 msec | Standard Deviation 7.27 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 16 hr Post dose | 0.9 msec | Standard Deviation 8.78 |
| Group 3: Placebo | Placebo-corrected CHFB in PR Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 6 hr Post dose | 0.7 msec | Standard Deviation 8.87 |
Comparison: Pre dose90% CI: [-10.3, -3]
Comparison: 0.5 hr Post dose90% CI: [-10.5, -4]
Comparison: 1 hr Post dose90% CI: [-8.8, -1.2]
Comparison: 1.5 hr Post dose90% CI: [-8.4, -1.6]
Comparison: 2 hr Post dose90% CI: [-6.6, -0.3]
Comparison: 2.5 hr Post dose90% CI: [-6.1, 0.3]
Comparison: 3 hr Post dose90% CI: [-7.7, -1.5]
Comparison: 4 hr Post dose90% CI: [-10.3, -3.8]
Comparison: 5 hr Post dose90% CI: [-6.9, 0.6]
Comparison: 6 hr Post dose90% CI: [-7.8, -0.6]
Comparison: 7 hr Post dose90% CI: [-8.1, -1.6]
Comparison: 8 hr Post dose90% CI: [-7.8, -1.1]
Comparison: 9 hr Post dose90% CI: [-9.3, -2.6]
Comparison: 10 hr Post dose90% CI: [-7.8, -1.1]
Comparison: 12 hr Post dose90% CI: [-7.3, -1.1]
Comparison: 16 hr Post dose90% CI: [-9.7, -2]
Comparison: 24 hr Post dose90% CI: [-12.5, -3.8]
Comparison: Pre dose90% CI: [-1.2, 5.9]
Comparison: 0.5 hr Post dose90% CI: [-4.5, 1.8]
Comparison: 1 hr Post dose90% CI: [-4, 3.3]
Comparison: 1.5 hr Post dose90% CI: [-3, 3.6]
Comparison: 2 hr Post dose90% CI: [-4, 2]
Comparison: 2.5 hr Post dose90% CI: [-2.6, 3.6]
Comparison: 3 hr Post dose90% CI: [-3.7, 2.3]
Comparison: 4 hr Post dose90% CI: [-5.4, 0.9]
Comparison: 5 hr Post dose90% CI: [-2.5, 4.6]
Comparison: 6 hr Post dose90% CI: [-4.1, 2.8]
Comparison: 7 hr Post dose90% CI: [-5, 1.3]
Comparison: 8 hr Post dose90% CI: [-3.7, 2.8]
Comparison: 9 hr Post dose90% CI: [-3.4, 3.1]
Comparison: 10 hr Post dose90% CI: [-2.8, 3.7]
Comparison: 12 hr Post dose90% CI: [-2.9, 3.1]
Comparison: 16 hr Post dose90% CI: [-3.1, 4.3]
Comparison: 24 hr Post dose90% CI: [-2.5, 5.9]
Secondary
Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10
The CHFB in QRS was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.
Time frame: Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose
Population: ECG population with available data was analyzed. ECG data was collected on Day 10, where participants received setmelanotide 3 mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1 hr Post dose | 0.5 msec | Standard Deviation 5.21 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 24 hr Post dose | -0.3 msec | Standard Deviation 5.38 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Pre dose | -0.2 msec | Standard Deviation 4.9 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 0.5 hr Post dose | 0.0 msec | Standard Deviation 3.85 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1.5 hr Post dose | -0.6 msec | Standard Deviation 3.69 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2 hr Post dose | 0.2 msec | Standard Deviation 4.04 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2.5 hr Post dose | 0.2 msec | Standard Deviation 4.41 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 3 hr Post dose | 0.7 msec | Standard Deviation 4.31 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 4 hr Post dose | 0.6 msec | Standard Deviation 3.95 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 5 hr Post dose | 0.5 msec | Standard Deviation 3.82 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 6 hr Post dose | 0.4 msec | Standard Deviation 4.71 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 7 hr Post dose | 0.9 msec | Standard Deviation 5.3 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 8 hr Post dose | 0.2 msec | Standard Deviation 4.23 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 9 hr Post dose | -0.2 msec | Standard Deviation 4.19 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 10 hr Post dose | 1.6 msec | Standard Deviation 4.23 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 12 hr Post dose | 0.8 msec | Standard Deviation 5.08 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 16 hr Post dose | 1.0 msec | Standard Deviation 4.77 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 8 hr Post dose | 1.1 msec | Standard Deviation 3.85 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1 hr Post dose | 0.8 msec | Standard Deviation 3.38 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 7 hr Post dose | 0.1 msec | Standard Deviation 3.66 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 4 hr Post dose | -0.7 msec | Standard Deviation 3.94 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 24 hr Post dose | 1.6 msec | Standard Deviation 4.53 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 16 hr Post dose | 1.5 msec | Standard Deviation 3.97 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Pre dose | 0.9 msec | Standard Deviation 3.42 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 5 hr Post dose | 1.0 msec | Standard Deviation 3.88 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 0.5 hr Post dose | 0.6 msec | Standard Deviation 6.31 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 9 hr Post dose | -0.1 msec | Standard Deviation 2.93 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1.5 hr Post dose | -0.2 msec | Standard Deviation 3.06 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 6 hr Post dose | -0.4 msec | Standard Deviation 3.92 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2 hr Post dose | 0.1 msec | Standard Deviation 3.37 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 12 hr Post dose | 1.9 msec | Standard Deviation 4.1 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2.5 hr Post dose | 0.5 msec | Standard Deviation 4.7 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 10 hr Post dose | 0.2 msec | Standard Deviation 3.95 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 3 hr Post dose | 0.4 msec | Standard Deviation 3.6 |
Comparison: Pre dose90% CI: [-2.6, 1.2]
Comparison: 0.5 hr post dose90% CI: [-2.6, 0.7]
Comparison: 1 hr post dose90% CI: [-1.1, 2.3]
Comparison: 1.5 hr post dose90% CI: [-1.5, 1.3]
Comparison: 2 hr post dose90% CI: [-0.8, 2.4]
Comparison: 2.5 hr post dose90% CI: [-1, 2.4]
Comparison: 3 hr post dose90% CI: [-1.6, 2]
Comparison: 4 hr post dose90% CI: [-0.9, 2.3]
Comparison: 5 hr post dose90% CI: [-1.2, 2.1]
Comparison: 6 hr post dose90% CI: [-0.7, 2.4]
Comparison: 7 hr post dose90% CI: [-0.6, 2.4]
Comparison: 8 hr post dose90% CI: [-1, 2.2]
Comparison: 9 hr post dose90% CI: [-1.6, 1.3]
Comparison: 10 hr post dose90% CI: [-1.5, 1.6]
Comparison: 12 hr post dose90% CI: [-0.2, 3]
Comparison: 16 hr post dose90% CI: [-0.3, 3.4]
Comparison: 24 hr post dose90% CI: [-2.1, 1.6]
Comparison: Pre dose90% CI: [-1.2, 2.6]
Comparison: 0.5 hr post dose90% CI: [-1.9, 1.4]
Comparison: 1 hr post dose90% CI: [-1.2, 2.2]
Comparison: 1.5 hr post dose90% CI: [-0.7, 2.1]
Comparison: 2 hr post dose90% CI: [-1.1, 2.2]
Comparison: 2.5 hr post dose90% CI: [-0.9, 2.5]
Comparison: 3 hr post dose90% CI: [-1.5, 2.1]
Comparison: 4 hr post dose90% CI: [-2.1, 1.1]
Comparison: 5 hr post dose90% CI: [-1.5, 1.9]
Comparison: 6 hr post dose90% CI: [-1.7, 1.4]
Comparison: 7 hr post dose90% CI: [-1.6, 1.4]
Comparison: 8 hr post dose90% CI: [-0.7, 2.4]
Comparison: 9 hr post dose90% CI: [-1.6, 1.3]
Comparison: 10 hr post dose90% CI: [-1.4, 1.6]
Comparison: 12 hr post dose90% CI: [-0.1, 3.1]
Comparison: 16 hr post dose90% CI: [-0.7, 3]
Comparison: 24 hr post dose90% CI: [-0.3, 3.4]
Secondary
Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16
The CHFB in QRS was analyzed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.
Time frame: Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose
Population: ECG population with available data was analyzed. ECG data was collected on Day 16, where participants received setmelanotide 7 mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 16 hr Post dose | 1.1 msec | Standard Deviation 2.9 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 3 hr Post dose | 0.5 msec | Standard Deviation 2.91 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Pre dose | 1.0 msec | Standard Deviation 4.11 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 4 hr Post dose | 0.7 msec | Standard Deviation 4.35 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 7 hr Post dose | 1.5 msec | Standard Deviation 4.92 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 5 hr Post dose | -0.2 msec | Standard Deviation 4.31 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 0.5 hr Post dose | 0.5 msec | Standard Deviation 3.57 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 8 hr Post dose | -0.2 msec | Standard Deviation 4.03 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 6 hr Post dose | -0.2 msec | Standard Deviation 4.63 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 9 hr Post dose | 0.2 msec | Standard Deviation 4.13 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1 hr Post dose | 0.9 msec | Standard Deviation 3.2 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 10 hr Post dose | 1.2 msec | Standard Deviation 3.19 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2 hr Post dose | -0.2 msec | Standard Deviation 3.97 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 12 hr Post dose | 1.4 msec | Standard Deviation 5.13 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1.5 hr Post dose | -0.8 msec | Standard Deviation 3.06 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 24 hr Post dose | 1.3 msec | Standard Deviation 4.68 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2.5 hr Post dose | 1.1 msec | Standard Deviation 2.95 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 24 hr Post dose | 0.5 msec | Standard Deviation 3.69 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1.5 hr Post dose | -0.4 msec | Standard Deviation 3.65 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 6 hr Post dose | 0.3 msec | Standard Deviation 2.99 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 7 hr Post dose | 0.7 msec | Standard Deviation 4.1 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 12 hr Post dose | -0.2 msec | Standard Deviation 4.74 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Pre dose | -0.8 msec | Standard Deviation 3.9 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 0.5 hr Post dose | 0.2 msec | Standard Deviation 3.9 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2 hr Post dose | 0.3 msec | Standard Deviation 3.41 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2.5 hr Post dose | -0.2 msec | Standard Deviation 4.2 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 3 hr Post dose | 1.0 msec | Standard Deviation 3.69 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 4 hr Post dose | 0.5 msec | Standard Deviation 2.93 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 5 hr Post dose | -1.4 msec | Standard Deviation 5.54 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 8 hr Post dose | 0.7 msec | Standard Deviation 2.77 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 9 hr Post dose | -0.4 msec | Standard Deviation 3.15 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 10 hr Post dose | -1.2 msec | Standard Deviation 2.73 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 16 hr Post dose | -0.7 msec | Standard Deviation 4.75 |
| Group 3: Placebo | Placebo-corrected CHFB in QRS Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1 hr Post dose | -1.0 msec | Standard Deviation 6.86 |
Comparison: Pre dose90% CI: [-1.3, 2.9]
Comparison: 0.5 hr post dose90% CI: [-1.8, 1.2]
Comparison: 1 hr post dose90% CI: [-1.4, 3.8]
Comparison: 1.5 hr post dose90% CI: [-1.8, 1.8]
Comparison: 2 hr post dose90% CI: [-3, 0.3]
Comparison: 2.5 hr post dose90% CI: [0, 3.1]
Comparison: 3 hr post dose90% CI: [-1.7, 1.5]
Comparison: 4 hr post dose90% CI: [-0.3, 2.9]
Comparison: 5 hr post dose90% CI: [-2.2, 2]
Comparison: 6 hr post dose90% CI: [-0.8, 2.3]
Comparison: 7 hr post dose90% CI: [-0.8, 2.7]
Comparison: 8 hr post dose90% CI: [-0.3, 2.4]
Comparison: 9 hr post dose90% CI: [-0.7, 2.9]
Comparison: 10 hr post dose90% CI: [-1.4, 1.9]
Comparison: 12 hr post dose90% CI: [-0.6, 3.2]
Comparison: 16 hr post dose90% CI: [-1, 2.4]
Comparison: 24 hr post dose90% CI: [-1, 4.2]
Comparison: Pre dose90% CI: [-2.3, 1.7]
Comparison: 0.5 hr post dose90% CI: [-1.6, 1.3]
Comparison: 1 hr post dose90% CI: [-3.8, 1.2]
Comparison: 1.5 hr post dose90% CI: [-1.7, 1.8]
Comparison: 2 hr post dose90% CI: [-2.7, 0.5]
Comparison: 2.5 hr post dose90% CI: [-0.8, 2.3]
Comparison: 3 hr post dose90% CI: [-1.3, 1.8]
Comparison: 4 hr post dose90% CI: [-1.2, 1.9]
Comparison: 5 hr post dose90% CI: [-3.5, 0.5]
Comparison: 6 hr post dose90% CI: [-0.6, 2.3]
Comparison: 7 hr post dose90% CI: [-1.3, 2.1]
Comparison: 8 hr post dose90% CI: [0, 2.6]
Comparison: 9 hr post dose90% CI: [-1.3, 2.2]
Comparison: 10 hr post dose90% CI: [-2.7, 0.5]
Comparison: 12 hr post dose90% CI: [-2.1, 1.5]
Comparison: 16 hr post dose90% CI: [-1.9, 1.4]
Comparison: 24 hr post dose90% CI: [-0.2, 4.9]
Secondary
Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10
The CHFB in QTcF was analyzed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.
Time frame: Baseline and Day 10: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose
Population: ECG population with available data was analyzed. ECG data was collected on Day 10, where participants received setmelanotide 3 mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 0.5 hr Post dose | -3.6 msec | Standard Deviation 9.83 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 6 hr Post dose | -0.4 msec | Standard Deviation 9.71 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2.5 hr Post dose | 1.2 msec | Standard Deviation 11.22 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 7 hr Post dose | 1.0 msec | Standard Deviation 8.02 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1.5 hr Post dose | -3.0 msec | Standard Deviation 9.53 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 8 hr Post dose | 2.6 msec | Standard Deviation 9.11 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 3 hr Post dose | 2.1 msec | Standard Deviation 10.06 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 9 hr Post dose | 4.1 msec | Standard Deviation 7.84 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1 hr Post dose | -2.9 msec | Standard Deviation 12.69 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 10 hr Post dose | 5.0 msec | Standard Deviation 8.14 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 4 hr Post dose | 2.0 msec | Standard Deviation 9.76 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 12 hr Post dose | 1.9 msec | Standard Deviation 9.25 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2 hr Post dose | -1.0 msec | Standard Deviation 11.26 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 16 hr Post dose | 1.7 msec | Standard Deviation 7.46 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 5 hr Post dose | 2.4 msec | Standard Deviation 9.38 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 24 hr Post dose | -0.7 msec | Standard Deviation 13.32 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Pre dose | 1.9 msec | Standard Deviation 7.82 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 24 hr Post dose | 6.6 msec | Standard Deviation 8 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | Pre dose | 1.5 msec | Standard Deviation 7.76 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 0.5 hr Post dose | -5.3 msec | Standard Deviation 8.75 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1 hr Post dose | -3.7 msec | Standard Deviation 9.39 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 1.5 hr Post dose | 0.9 msec | Standard Deviation 8.56 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2 hr Post dose | 2.0 msec | Standard Deviation 8.74 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 2.5 hr Post dose | 4.9 msec | Standard Deviation 8.75 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 3 hr Post dose | 4.9 msec | Standard Deviation 7.39 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 4 hr Post dose | 6.3 msec | Standard Deviation 8.63 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 5 hr Post dose | 8.1 msec | Standard Deviation 8.42 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 6 hr Post dose | 6.0 msec | Standard Deviation 6.61 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 7 hr Post dose | 5.1 msec | Standard Deviation 8.39 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 8 hr Post dose | 4.4 msec | Standard Deviation 8.18 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 9 hr Post dose | 5.0 msec | Standard Deviation 10.47 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 10 hr Post dose | 6.2 msec | Standard Deviation 6.85 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 12 hr Post dose | 8.7 msec | Standard Deviation 4.84 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 10 | 16 hr Post dose | 5.9 msec | Standard Deviation 8.09 |
Comparison: Pre dose90% CI: [0.1, 6.8]
Comparison: 0.5 hr Post dose90% CI: [-3, 4.6]
Comparison: 1 hr Post dose90% CI: [-4.1, 3.9]
Comparison: 1.5 hr Post dose90% CI: [-2.7, 4.4]
Comparison: 2 hr Post dose90% CI: [-0.6, 6.6]
Comparison: 2.5 hr Post dose90% CI: [-0.3, 7.4]
Comparison: 3 hr Post dose90% CI: [1.2, 8.1]
Comparison: 4 hr Post dose90% CI: [1.5, 8.9]
Comparison: 5 hr Post dose90% CI: [-1.7, 5.8]
Comparison: 6 hr Post dose90% CI: [-1.6, 5.1]
Comparison: 7 hr Post dose90% CI: [-1.1, 5.7]
Comparison: 8 hr Post dose90% CI: [-1.4, 6.2]
Comparison: 9 hr Post dose90% CI: [0.9, 7.8]
Comparison: 10 hr Post dose90% CI: [0.3, 7.4]
Comparison: 12 hr Post dose90% CI: [-4.2, 2.7]
Comparison: 16 hr Post dose90% CI: [0.1, 7]
Comparison: 24 hr Post dose90% CI: [-5.7, 2.8]
Comparison: Pre dose90% CI: [-1, 5.6]
Comparison: 0.5 hr Post dose90% CI: [-5.4, 2.2]
Comparison: 1 hr Post dose90% CI: [-3.8, 4.3]
Comparison: 1.5 hr Post dose90% CI: [0.4, 7.6]
Comparison: 2 hr Post dose90% CI: [2.7, 10]
Comparison: 2.5 hr Post dose90% CI: [2.6, 10.2]
Comparison: 3 hr Post dose90% CI: [5, 12]
Comparison: 4 hr Post dose90% CI: [6.4, 13.8]
Comparison: 5 hr Post dose90% CI: [4.1, 11.6]
Comparison: 6 hr Post dose90% CI: [4.4, 11.2]
Comparison: 7 hr Post dose90% CI: [3.4, 10.2]
Comparison: 8 hr Post dose90% CI: [0.6, 8.3]
Comparison: 9 hr Post dose90% CI: [3.1, 10]
Comparison: 10 hr Post dose90% CI: [3, 10.1]
Comparison: 12 hr Post dose90% CI: [1.8, 8.8]
Comparison: 16 hr Post dose90% CI: [3.7, 10.6]
Comparison: 24 hr Post dose90% CI: [-1, 7.5]
Secondary
Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16
The CHFB in QTcF was analysed using an ANOVA including treatment, time and their interaction as main factors and structuring the residual matrix in order to account for the repeated measurement pattern of the data. HR was considered as covariate.
Time frame: Baseline and Day 16: Pre dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10,12, 16, 24 hrs postdose
Population: ECG population with available data was analyzed. ECG data was collected on Day 16, where participants received setmelanotide 7 mg.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 4 hr Post dose | 3.6 msec | Standard Deviation 9.88 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1.5 hr Post dose | 0.3 msec | Standard Deviation 10.42 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 5 hr Post dose | 4.7 msec | Standard Deviation 9.41 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 0.5 hr Post dose | 1.0 msec | Standard Deviation 8.83 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 6 hr Post dose | 2.8 msec | Standard Deviation 9.64 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2 hr Post dose | 2.2 msec | Standard Deviation 10.94 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 7 hr Post dose | 1.5 msec | Standard Deviation 11.14 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Pre dose | 4.5 msec | Standard Deviation 6.49 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 8 hr Post dose | 2.8 msec | Standard Deviation 10.02 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2.5 hr Post dose | 2.7 msec | Standard Deviation 11.61 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 9 hr Post dose | 6.1 msec | Standard Deviation 8.72 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1 hr Post dose | 1.6 msec | Standard Deviation 9.18 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 10 hr Post dose | 6.5 msec | Standard Deviation 6.64 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 3 hr Post dose | 4.3 msec | Standard Deviation 11.34 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 12 hr Post dose | 5.8 msec | Standard Deviation 7.96 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 24 hr Post dose | 1.0 msec | Standard Deviation 11.26 |
| Group 1: Setmelanotide 3 mg | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 16 hr Post dose | 1.4 msec | Standard Deviation 7.77 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 24 hr Post dose | 4.4 msec | Standard Deviation 10.57 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 16 hr Post dose | 6.6 msec | Standard Deviation 8.51 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | Pre dose | -0.8 msec | Standard Deviation 8.3 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 0.5 hr Post dose | -1.8 msec | Standard Deviation 5.93 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1 hr Post dose | -1.9 msec | Standard Deviation 7.49 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 1.5 hr Post dose | 3.0 msec | Standard Deviation 7.05 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2 hr Post dose | 4.2 msec | Standard Deviation 7.53 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 2.5 hr Post dose | 7.6 msec | Standard Deviation 8.45 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 3 hr Post dose | 8.1 msec | Standard Deviation 8.19 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 4 hr Post dose | 8.8 msec | Standard Deviation 6.37 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 5 hr Post dose | 7.5 msec | Standard Deviation 8.97 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 6 hr Post dose | 8.5 msec | Standard Deviation 6.18 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 7 hr Post dose | 9.1 msec | Standard Deviation 7.29 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 8 hr Post dose | 8.0 msec | Standard Deviation 5.73 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 9 hr Post dose | 7.0 msec | Standard Deviation 7.33 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 10 hr Post dose | 7.0 msec | Standard Deviation 9.93 |
| Group 3: Placebo | Placebo-corrected CHFB in QTcF Intervals After Administration of SC Setmelanotide or Oral Moxifloxacin at Day 16 | 12 hr Post dose | 10.8 msec | Standard Deviation 9.14 |
Comparison: Pre dose90% CI: [3.7, 11.8]
Comparison: 0.5 hr Post dose90% CI: [3.3, 9.8]
Comparison: 1 hr Post dose90% CI: [0.6, 8.6]
Comparison: 1.5 hr Post dose90% CI: [0.6, 8.6]
Comparison: 2 hr Post dose90% CI: [-0.4, 8]
Comparison: 2.5 hr Post dose90% CI: [1.8, 10.4]
Comparison: 3 hr Post dose90% CI: [1.7, 9.8]
Comparison: 4 hr Post dose90% CI: [2.5, 9.8]
Comparison: 5 hr Post dose90% CI: [1.6, 9.8]
Comparison: 6 hr Post dose90% CI: [1.1, 8.4]
Comparison: 7 hr Post dose90% CI: [-0.9, 7]
Comparison: 8 hr Post dose90% CI: [1.3, 8.8]
Comparison: 9 hr Post dose90% CI: [2.5, 10.6]
Comparison: 10 hr Post dose90% CI: [4.8, 12.3]
Comparison: 12 hr Post dose90% CI: [4.4, 11.4]
Comparison: 16 hr Post dose90% CI: [0.9, 8.9]
Comparison: 24 hr Post dose90% CI: [3.6, 12]
Comparison: Pre dose90% CI: [-1.8, 6]
Comparison: 0.5 hr Post dose90% CI: [0, 6.2]
Comparison: 1 hr Post dose90% CI: [-1.9, 5.7]
Comparison: 1.5 hr Post dose90% CI: [2.6, 10.4]
Comparison: 2 hr Post dose90% CI: [1.3, 9.3]
Comparison: 2.5 hr Post dose90% CI: [7, 15.1]
Comparison: 3 hr Post dose90% CI: [5.9, 13.6]
Comparison: 4 hr Post dose90% CI: [7.2, 14.2]
Comparison: 5 hr Post dose90% CI: [4.9, 12.7]
Comparison: 6 hr Post dose90% CI: [7.5, 14.5]
Comparison: 7 hr Post dose90% CI: [7.1, 14.6]
Comparison: 8 hr Post dose90% CI: [7.6, 14.9]
Comparison: 9 hr Post dose90% CI: [5.9, 13.7]
Comparison: 10 hr Post dose90% CI: [6.9, 14.1]
Comparison: 12 hr Post dose90% CI: [8.4, 15.2]
Comparison: 16 hr Post dose90% CI: [5.6, 13.3]
Comparison: 24 hr Post dose90% CI: [6.8, 14.9]